The oxygen carrying capacity and lack of toxicity of perfluorinated liquids has long been established. Emulsions of fluorocarbon liquids were also used as artificial bloods. U.S. Pat. No. 3,911,138 which issued to Leland C. Clark, Jr., sets forth the various advantages and needs for artificial blood and may be referred to as further background of this invention. In that Clark patent, artificial bloods containing perfluorocyclocarbons were disclosed as useful blood substitutes. Emulsions containing emulsified particles of the perfluorocyclocarbons were also infused intravenously into experimental animals and functioned as oxygen-carbon dioxide carrying agents intravascularly. The perfluorocyclocarbons disclosed in that Clark patent were referred to as RES-phobic, which indicated that the perfluorocyclocarbons exhibited a unique property of temporary sequestration by the liver or spleen and subsequent elimination by the animal body. It was later disclosed in U.S. Pat. No. 4,150,798 which issued to Leland C. Clark, Jr. et al, that certain other perfluoropolycyclic compounds were useful as synthetic blood in perfusion media. The perfluorinated polycyclic compounds disclosed in this patent are known generally as bicyclononanes and adamantanes. Further improvements have been reported in the patent art as disclosed in U.S. Pat. No. 4,443,480 which issued to Leland C. Clark, Jr. and is directed to oxygen transport agents containing a perfluorocyclocarbon and an organoamine oxide.
The brief reference to patents herein is intended only as background information leading up to this invention and is not intended to be exhaustive of the patent art. On the literature side of the prior art, reference may be made to such articles as "The Synthesis and Biological Screening of New and Improved Fluorocarbon Compounds for Use as Artificial Blood Substitutes", Final Report prepared under Contract No. 1HB6-2927 for the period Jun. 30, 1976-Dec. 31, 1978 by Robert E. Moore, Principal Investigator, as prepared for the National Institutes of Health. In this report, a number of fluorocarbons were reported as having been evaluated biologically for use in experimental animals. The biological evaluations were performed under the direction of Leland C. Clark, Jr., Ph.D. Among the approximately thirty fluorocarbons reported upon was bicyclo[4.3.0.] nonane, or otherwise known as perfluoroindane. However, perfluorindane was not considered to be viable choice, principally because it had a high vapor pressure of 32.8 mm at 37.degree. C. This value was the highest among the perfluorinated hydrocarbons reported upon in the above NIH report. It was then believed that such a high vapor pressure would cause gas embolism, consistent with earlier reports in Clark U.S. Pat. No. 3,911,138 for other analogous carbon-containing perfluorocyclo derivatives such as perfluorotrimethylcyclohexane and perfluoroisopropylcyclohexane. In the event emulsions containing such perfluorocyclohexanes were used, then breathing the vapor of the fluorocarbons, or similar fluorocarbons, that were injected balances the gas pressures in the lungs so that gas embolism does not occur. Without this gas or vapor breathing, partial pressure of the fluorocarbons in the lungs is, unlike most other gases and vapors, extremely low apparently due primarily to the poor solubility of the fluorocarbon in the blood; and its slow diffusion from the blood through the lung membrane. Hence, the total gas pressure in the blood exceeds total alveolar pressure, and gas embolism results which could lead to death in a short time. Thus, perfluorocyclocarbons that have lower vapor pressures than perfluorocyclohexanes were considered critically necessary in order to avoid special precautions or detrimental gas embolism.
About ten years has elapsed since the above mentioned NIH report upon the use of perfluorocarbons as oxygen transporting agents in animals. More recently, it has been reported by Kouichi Yamanouchi et al in Chem. Parm. Bull., 33(3)1221-1231(1985) entitled "Quantitative Structure in Vivo Half-Life Relationships of Perfluorochemicals for Use as Oxygen Transporters" that a series of perfluorochemicals were investigated in terms of their quantitative structure-activity relationships. Among other findings reported in this paper, it was concluded that the vapor pressure of perfluorocarbons apparently plays an important role in the excretion system and it must be controlled within an acceptable limit so as not to cause lung damage.